Abstract

Addressing the transmission enigma of the neglected disease Buruli ulcer (BU) is a World Health Organization priority. In Australia, we have been building a hierarchy of evidence implicating mosquitoes in transmission. Here we tested a contaminated skin model of BU transmission by dipping the tails from healthy mice in cultures of the causative agent, Mycobacterium ulcerans. Tails were exposed to mosquito blood feeding or punctured with sterile needles. Two of 11 of mice with M. ulcerans contaminated tails exposed to feeding mosquitoes developed BU. Eighteen of 20 mice subjected to contaminated tail needle puncture developed BU. Mouse tails coated only in bacteria did not develop disease. We observed a low infectious dose-50 of four colony-forming units and a median incubation time of 12 weeks, overlapping data from human infections. We have uncovered a highly efficient and biologically plausible atypical transmission mode of BU via natural or anthropogenic skin punctures.